Emergence of Linezolid-ResistantStaphylococcus aureusafter Prolonged Treatment of Cystic Fibrosis Patients in Cleveland, Ohio

Abstract

ABSTRACTLinezolid (LZD)-resistantStaphylococcus aureus(LRSA) isolates were monitored from 2000 to 2009 in Cleveland, OH. LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, with 11 LRSA-infected CF patients being identified by 2009. LRSA was isolated from 8 of 77 CF patients withS. aureusrespiratory tract infection treated with LZD from 2000 to 2006. Analysis of clinical data showed that the 8 CF patients with LRSA received more LZD courses (18.8 versus 5.9;P= 0.001) for a longer duration (546.5 versus 211.9 days;P< 0.001) and had extended periods of exposure to LZD (83.1 versus 30.1 days/year;P< 0.001) than the 69 with LZD-susceptible isolates. Five LRSA isolates included in the clinical analysis (2000 to 2006) and three collected in 2009 were available for molecular studies. Genotyping by repetitive extrapalindromic PCR and pulsed-field gel electrophoresis revealed that seven of these eight LRSA strains from unique patients were genetically similar. By multilocus sequence typing, all LRSA isolates were included in clonal complex 5 (seven of sequence type 5 [ST5] and one of ST1788, a new single-locus variant of ST5). However, seven different variants were identified byspatyping. According to theEscherichia colinumbering system, seven LRSA isolates contained a G2576T mutation (G2603T,S. aureusnumbering) in one to four of the five copies of domain V of the 23S rRNA genes. One strain also contained a mutation (C2461T,E. colinumbering) not previously reported. Two strains, including one without domain V mutations, possessed single amino acid substitutions (Gly152Asp or Gly139Arg) in the ribosomal protein L3 of the peptidyltransferase center, substitutions not previously reported in clinical isolates. Emergence of LRSA is a serious concern for CF patients who undergo prolonged courses of LZD therapy.